Method for obtaining oxacarbonyl polymers, functionalization, resulting polymers and functionalizing agent

ABSTRACT

The invention concerns a method for obtaining oxacarbonyl polymers comprising steps which consist in: providing at least monomers comprising at least a cyclic oxacarbonyl function, an initiator, and in polymerising or copolymerising said monomers, in bulk or in solution, the initiator being selected among bicyclic guanidine compounds of formula (I) or (II) wherein one and/or the other of the cycles can be substituted, in at least any one of positions 2, 3, 4, 8, 9 and 10 of formula (I) or in at least any one of positions 2, 3, 7 and 8 of formula (II), by at least a radical selected among the alkyl groups with 1 to 6 carbon atoms, the cycloalkyl groups with 5 to 7 carbon atoms, polystyrene hydrocarbon chains.

The invention relates to a process for producing oxacarbonylatedpolymers by opening rings and polymerization of monomers comprising atleast one cyclic oxacarbonyl function, such as a lactone function.

Lactones have a known capacity to polymerize, under reaction conditionsand according to mechanisms which vary essentially depending on thestarting lactone monomer and on the catalyst or initiator used. In orderto initiate polymerization by opening rings, the prior art teaches adiversity of initiators; thus, the latter may be anionic in nature, suchas a hydride, a carbanion, an alkoxide, a thiolate or an alkali metal,alkaline earth metal, aluminum, zinc or tin carboxylate; it may benucleophilic and uncharged in nature, such as a tertiary amine forpolymerization of β-propiolactone, or a phosphine; it may also be chosenfrom protic compounds such as carboxylic acids, alcohols, glycols, orpolar functions such as primary and secondary amines and combinations ofstructures such as alkanolamines, or from coordination complexes, suchas those of aluminum.

In general, the polymerization reaction is carried out in totallyanhydrous medium, in an inert solvent, at a temperature which mustsometimes exceed 150° C.

Polymerization conditions known to date produce, however, greatvariability of polymerization yields and of the polymolecularity andpolydispersity indices for the polymer obtained, depending on thestarting monomer. In addition, the known initiators are oftenundesirable and/or toxic.

The present invention provides a process for producing oxacarbonylatedpolymers from monomers comprising at least one cyclic oxacarbonylfunction, and in particular a lactone function, making it possible,under gentle reaction conditions, to obtain complete consumption of thestarting monomer(s).

Specifically, according to the process of the invention, firstly, atemperature close to room temperature is often sufficient to polymerizecertain lactones, for which the reaction requires high temperaturesusing known polymerization processes, and, secondly, polymers which,after washing, are free of starting monomers and of initiator areproduced, which makes them very easy to isolate and makes it possible toenvision using them in very varied applications, including those inwhich it is essential to have a pure polymer.

The process of the invention comprises the following steps:

At least a monomer comprising at least one cyclic oxacarbonyl function,and an initiator, are available,

The polymerization or copolymerization of said monomer is carried out inbulk or in solution,

The initiator being chosen from the bicyclic guanidine compoundscorresponding to formula (I) or formula (II)

in which one and/or the other of the rings may be substituted, in atleast any one of positions 2, 3, 4, 8, 9 and 10 of formula (I) or in atleast any one of positions 2, 3, 7 and 8 of formula (II), with at leastone radical chosen from alkyl groups having from 1 to 6 carbon atoms,cycloalkyl groups having from 5 to 7 carbon atoms and thehydrocarbon-based chains of polystyrene.

An oxacarbonyl function is intended to mean a function —O—CO— includedin a ring, the monomer therefore comprising at least one oxygenatedheterocycle. By way of example, it may be a lactone function.

A preferred initiator corresponds to formula (I) and is7H-1,5,7-triazabicyclo[4.4.0]dec-5-ene (hereinafter denoted TBD).

As mentioned above, the monomer(s) may comprise at least one lactonefunction; they are then advantageously chosen from the group consistingof ε-caprolactone, δ-valerolactone, β-butyrolactone, γ-butyrolactone,2,6-dimethyl-1,4-dioxan-2,5-dione (or lactide) and 1,4-dioxan-2,5-dione(or glycolide).

Depending on the choice of starting monomer(s), the process leads to theproduction of a homopolymer if only one monomer is available, or of acopolymer, the latter possibly being a block copolymer or a randomcopolymer, if at least two different monomers are reacted.

The preferential reaction conditions of the process according to theinvention are stated hereinafter, and they should be considered alone orin combination:

the molar ratio of the monomer(s) to the initiator ranges from 1 to 500,advantageously from 1 to 200,

the reaction is carried out at a temperature ranging from 0° C. to 150°C., preferably from 50° C. to 120° C.,

the reaction is carried out in bulk; it may also be carried out in asolvent, in particular chosen from tetrahydrofuran (THF), toluene,acetone and dibutyl ether,

the reaction duration ranges from 10 minutes to 12 hours.

A subject of the present invention is an oxacarbonylated polymer whichcan be produced using the production process defined above.

The process of the invention also has the advantage of making itpossible to functionalize the polymers obtained in situ, directly in thereaction mixture, so as to produce activated or activatable polymersmodified by functionalization. This functionalization is carried outusing a functionalizing agent and, depending on the intended purpose ofthe polymer, this functionalization may be particularly advantageous. Byway of illustration, after functionalization, biodegradable modifiedpolylactones are produced, having the properties of an agent whichmodifies the viscosity of organic solvents and aqueous media, includingwater.

A functionalizing agent according to the invention is preferably alinear or branched molecule or macromolecule comprising at least onealcohol or amine function.

This agent may be selected from:

pure functionalizing compounds, such as butanol, ethoxyethanol,pentraerythritol, allylamine, methoxyethylamine, decylamine,ethoxyethanolamine and esters of carboxylic acids,

functionalized polymers, for instance polymers and copolymers, such aspolymers and copolymers of alkylene glycol, and especially polymers andcopolymers of ethylene glycol, in particular copolymers of ethyleneglycol (PEG) and of propylene glycol (PPG), mixtures of said polymers,mixtures of said copolymers, mixtures of said polymers and copolymers,polyalkyleneamines such as Jeffamines®, polyesters such as polyethyleneterephthalates, and mixtures thereof,

with natural products such as polyglucosides and, by way of example,gums, dextrans, chitosans and starch, and from mixtures of these agents,and

mixtures of the abovementioned agents: by way of example, the mixturecomprising at least one ethylene glycol polymer and at least onepolyglucoside may be chosen.

Gums, such as xanthan gum and guar gum, optionally mixed with anotherfunctionalizing agent, such as an alkylene glycol polymer, constituteparticularly advantageous agents.

The polymerization and the functionalization may be carried outsequentially or they may be carried out in situ simultaneously, in bulkor in the solvent.

Thus, the invention relates to a process for producing oxacarbonylatedpolymers, as defined above, according to which a functionalizing agentis added to the monomer and to the initiator, according to an in situmethod or a sequenced method. A preferred agent is chosen from theagents listed above.

A subject of the invention is also an agent for functionalizing anoxacarbonylated polymer, which comprises at least one gum, such as axantham or guar gum, combined with at least one polymer and/or onecopolymer of alkylene glycol oxide, such as the polymers and copolymersof ethylene glycol oxide (PEG).

The invention also relates to a functionalized oxacarbonylated polymerwhich can be produced using the polymerization a nd functionalizationprocess defined above.

Another subject of the invention is the use of a bicyclic guanidinecompound corresponding to formula (I) or (II) mentioned and describedabove, for initiating the reaction of polymerization or ofcopolymerization with the action of monomers comprising at least onecyclic oxacarbonylated function. Advantageously, the bicyclic guanidinecompound is TBD.

According to a variant of use of the initiator of the invention, thelatter is attached directly or indirectly, or deposited, onto a solidsupport. By way of example, a suitable support is mineral or organic andconsists of a resin, a polymer such as a polystyrene or a polypropylene,a copolymer such as a polystyrene/divinylbenzene copolymer, silica,clay, diatomite, zeolite, alumina or aluminosilicate. The expression“directly or indirectly” is intended to mean that said agent comprises,at least on one of its rings, a radical capable of binding to saidsupport, or a radical which will be bound to said support via a couplingarm. The latter is generally a hydrocarbon-based chain. The term“deposited” is intended to mean that said initiator is adsorbed onto anorganic or mineral support.

The present invention is illustrated hereinafter by Examples, 1 to 12,with the support of the diagram comprising FIGS. 1 to 5.

FIG. 1 represents the viscosity (in Pa.s⁻¹ of the reaction mediumdescribed in Example 1.5 as a function of time (in second)

FIG. 2 represents the viscosity (in Pa.s of the reaction mediumdescribed in Example 1.6 as a function of time (in seconds)

FIG. 3 illustrates the rheological behavior of a polycaprolactone afterfuntionalization according to Example 9.5, by representing the shearstrain (in Pa) as a function of the shear rate (in second⁻¹):

(a) solution at an aquaeous concentration of 6%

(b) solution at an aquaeous concentration of 4%.

FIG. 4 illustrates the rheofluidizing properties of the guar gum before(initial or unmodified guar) and after functionalization (modified guar)of the ε-polycaprolactone according to Example 9.5, by representing theshear strain (in Pa) as a function of the shear rate (second⁻¹):

(a) unmodified guar at an aqueous concentration of 1% by weight

(b) unmodified guar at an aqueous concentration of 0.5%

(c) modified guar at an aqueous concentration of 2.5%

(d) modified guar at an aqueous concentration of 1%.

EXAMPLE 1 Preparation of Polyesters According to the Invention UsingVarious Lactones

The polyesters produced correspond to the following formula:

R—[CO—(C_(α)H₂—C_(β)H₂—C_(γ)H₂—C_(δ)H₂—C_(ε)H₂)]_(n−1)—O—CO—CH₂—CH₂—CH₂—CH₂—CH₂OH

in which n represents the polymolecularity index and R represents agroup chosen from the guanidine group (TBD); OR′ in which R′ representsH or an alkyl group determined according to the alcohol selected at theend of the reaction; an acid function COOH; an ester function CHCOOR″;an amide function CHCONHR″ in which R″ is an alkyl group respectivelydetermined according to the alcohol or the amine used at the end of thereaction.

1.1—Preparation of the homopolymer 3600-polycaprolactone

57 g (0.5 mol) of ε-caprolactone are introduced into a 100 mlthree-necked reactor under nitrogen and 13.9 g of solid TBD (0.1 mol)are added, the monomer/initiator (M/I) molar ratio being equal to 5. Theinitiator completely dissolves with stirring and the reaction isexothermic. The temperature reaches 75° C. The mixture is stirred at 500rpm for 20 minutes. The viscose mixture is then brought to 80° C. forthree hours, then to 100° C. for one hour and finally to 120° C. for oneand a half hours.

The crude product is characterized by spectral analyses and stericexclusion chromatography (SEC) with THF.

Specifically, the NMR analysis indicates the unresolved peakscharacteristic of polycaprolactones at δ in ppm of 1.4 CH₂ γ; 1.65 CH₂(δ, β) ; 2.31 CH₂ α (triplet); 4.06 CH₂ ε (triplet). The CH₂OH chain endappears at ε_(T)=3.62 ppm (triplet). The NMR spectrum gives apolymolecularity index of 30.

The molecular mass measured by SEC (solvent THF, polystyrene internalreference) is Mn=3675 and Mw=12050; the Mn/Mw ratio=3.28.

The presence of the initiator is completely detectable by NMR, at δ=2.22and 3.34 ppm (in the form of unresolved peaks).

The polymer may be obtained free of traces of initiator if necessary, bydissolving the polymer in a solvent, such as methylene chloride ortoluene, followed by extraction with acidified water. 200 ml of CH₂Cl₂and 200 ml of an aqueous solution of acetic acid diluted at 2% are addedto the viscose mixture. The mixture is allowed to settle and the organicphase is isolated. This is washed with 100 ml of water containing 2% ofHCl and then again with pure water, and the organic phase is dried.

55 g of pure polycaprolactone identical to an authentic sample areisolated. No trace of monomer is detectable by NMR or by SEC.

1.2—Preparation of the homopolymer 5500-polycaprolactone

The procedure described above in 1.1 is repeated for an M/I molar ratioof 10, with 57 g (0.5 mol) of ε-caprolactone and 6.95 g (0.05 mol) ofTBD.

The reaction is exothermic and the mixture becomes viscose afterstirring for fifteen minutes.

The same protocol for synthesis as that described in 1.1 produces thecrude polycaprolactone and then the polycaprolactone purified bywashing.

The mean molecular masses obtained by SEC (THF) are: Mn=5500 andMw=20900, Mn/Mw=3.80.

1.3—Preparation of the homopolymer 30000-polycaprolactone

The procedure described above in 1.1 is repeated for an M/I molar ratioof 40, with 57 g (0.5 mol) of ε-caprolactone and 1.73 g (0.0125 mol) ofTBD.

The reaction is exothermic and the mixture becomes viscose afterstirring for fifteen minutes.

The same protocol for synthesis as that described in 1.1 produces thecrude polycaprolactone and then the polycaprolactone purified bywashing.

The proton NMR analysis indicates a polymolecularity index of 230. Themean molecular masses obtained by SEC (THF) are: Mn=34000 and Mw=49400,Mn/Mw=1.32.

1.4—Preparation of the homopolymer 30000-polycaprolactone

The procedure described above in 1.1 is repeated for an M/I molar ratioof 185, with 57 g (0.5 mol) of ε-caprolactone and 0.38 g (0.0027 mol) ofTBD.

The proton NMR analysis indicates a polymolecularity index of 230. Themean molecular masses obtained by GPC (THF) are: Mn=30700 and Mw=62000,Mn/Mw=2.02.

1.5—Preparation of the homopolymer 15000-polycaprolactone

The polymerization of ε-caprolactone is carried out for an M/I molarratio of 100, in the disk-shaped gaps of a rheometrix at the temperatureof 80° C.

The increase in viscosity is visualized on FIG. 1. The viscose plateauis reached after 4500 seconds of contact. The viscosity value is then1100

The ¹H NMR analysis of the sample gives a polymolecularity index of 98.The mean molecular masses obtained by SEC (THF) are Mn=15000 andMw=29000, Mn/Mw=1.95.

1.6—Preparation of the homopolymer 26000-polycaprolactone

The polymerization of ε-caprolactone is carried out for an M/I molarratio of 200, in the disk-shaped gaps of a rheometrix at the temperatureof 100° C.

The increase in viscosity is visualized on FIG. 2. The viscose plateauis reached after 4500 seconds of contact. The viscosity value is then21,00 Pa.s⁻¹.

The ¹H NMR analysis of the sample gives a polymolecularity index of 150.The mean molecular masses obtained by GPC (THF) are Mn=26000 andMw=46000, Mn/Mw=1.79.

EXAMPLE 2 Preparation of the Homopolymer polyvalerolactone According tothe Invention Using δ-valerolactone

The polymer produced corresponds to the following formula:

—[CO—(C_(α)H₂—C_(β)H₂—C_(γ)H₂—C_(δ)H₂)]_(n−1)—O—CO—CH₂—CH₂—CH₂—CH₂—CH₂OH

in which n represents the polymolecularity index.

The composition of the reaction mixture is as follows: 3.45 g (0.0345mol) of δ-valerolactone and 0.48 g (0.00345 mol) of TBD in 15 ml ofanhydrous THF.

The reaction is exothermic and the mixture becomes viscose afterstirring for fifteen minutes.

The proton NMR analysis indicates a polymolecularity index of 30. Theunresolved peaks characteristic of polyvalerolactones at δ in ppm are1.68 CH₂ δ, β; 2.32 CH₂ α; 4.1 CH₂ δ(triplet) [lacuna]. The CH₂OH chainend appears at δ=3.62 ppm (triplet).

EXAMPLE 3 Preparation of Copolymers Using δ-valerolactone andε-caprolactone

The reaction conditions are identical to those given in Example 1.1,with a mixture of 51.3 g of ε-caprolactone (0.45 mol) and 5 g ofδ-valerolactone (0.05 mol). The M/I molar ratio is 20.

The NMR spectrum of the copolymer produced shows an absence of thestarting monomers and is in accordance with the expected polymer.

The GPC indicates a single distribution Mn=31000 and Mw=10600; the Mn/Mwratio=3.4.

EXAMPLE 4 Preparation of a Polylactide Homopolymer Using d,l-lactide (or2,6-dimethyl-1,4-dioxan-2,5-dione)

20 ml of anhydrous toluene are introduced into a 50 ml three-neckedflask. A mixture of 3.26 g (0.0227 mol) of lactide and 0.315 g (0.00227mol) of TBD is added; the M/I molar ratio is 10. The temperature isbrought to 110° C. for 4 hours. Washing of the organic phase with 2%acetic acid then with 2% hydrochloric acid and then with water, followedby evaporation of the solvent, produces the pure polylactide identifiedby ¹H NMR: δ=1.55 ppm CH₃ (doublet); δ=5.17 CH broad peak; δ=4.36 ppm CH(quartet).

The degree of polymolecularity determined by NMR is 10. The polymercontains less than 3% of residual monomer. The mean molecular massesobtained by GPC (THF) are: Mn=2140 and Mw=4990, Mn/Mw=2.33.

EXAMPLE 5 Preparation of an ε-caprolactone Homopolymer in THF

The reaction is carried out in solution in THF at 60° C. 1.06 g of TBDare placed in 10 ml of solvent and then 33 g of ε-caprolactone dissolvedin 30 ml of solvent are added dropwise. The reaction mixture is broughtto the reflux temperature of THF for 180 minutes with stirring at 500rpm, and is then poured into 100 ml of water. An emulsion forms. Thereaction solvent is driven off and replaced with 100 ml of CH₂Cl₂. Theorganic phase is settled out and washed with 100 ml of water containing2% HCl and then with pure water, and the solvent is eliminated. Thepolycaprolactone is identified free of monomer.

EXAMPLE 6 Preparation of an ε-caprolactone-d,l-lactide Random Copolymer

The random copolymer ε-caprolactone(C)-d,l-lactide(L) may be representedby CLCLCLCLCLCCLCLL-etc.

14.4 g (0.1 mol) of d,l-lactide, 11.4 g (0.1 mol) of ε-caprolactone and1.39 g of solid TBD (0.01 mol) are introduced into a 100 ml three-neckedreactor under nitrogen. The M/I molar ratio is equal to 20. Theinitiator completely dissolves with stirring and the reaction isexothermic. The temperature reaches 50° C. The mixture is stirred at 500rpm for 30 minutes. The viscose mixture is then brought to 60° C. forone hour and then to 80° C. for three hours.

The NMR analysis indicates the resolved peaks α, β, γ, δ and ε of thepolymerized lactone accompanied by the unresolved peaks characteristicof the polymerized d,l-lactide. The mean mass composition of thecopolymer is 50 units of ε-caprolactone for 38 units of d,l-lactide.

The presence of a random copolymer is proved by ¹³C NMR, comparing theNMR spectra of the homopolymers and of the copolymer formed. The LC andCL sequences of the C═Os give δs in the range δ=170-173 ppm, whereas thecorresponding homopolymers are at δ=173.3 ppm for the C═O of thepolycaprolactone and δ=169-169.8 ppm for the C═O of the d,l-polylactide.This distribution is confirmed by the localized chemical shifts of the¹³Cs of the CHs and CH₂s for the same homopolymers and copolymers.

EXAMPLE 7 Preparation of an ε-caprolactone-d,l-lactide Block Copolymer,in Solution in THF

The block copolymer ε-caprolactone(C)-d,l-lactide(L) may be representedby CCCCC-LLLLL.

14.4 g (0.1 mol) of ε-caprolactone and 1.39 g (0.01 mol) of solid TBDare introduced into a 100 ml three-necked reactor under nitrogen. Thereaction mixture is brought to 80° C. for two hours and 11.4 g (0.1 mol)of d,l-lactide are added. The initial M/I molar ratio is equal to 10.The polymerization is continued for three hours at 80° C. The viscosemixture is isolated and purified according to the conventional method.

The NMR analysis indicates the unresolved peaks α, β, γ, δ and ε of thepolymerized lactone accompanied by the peaks characteristic of thepolymerized d,l-lactide at δ=1.38 ppm (multiplet); 4.40 ppm (quartet)and 5.17 ppm (unresolved peak). The mean composition by mass of thecopolymer is 42 units of ε-caprolactone for 28 (56 OCH(CH₃)CO fragments)of d,l-lactide.

The formation of a block copolymer is visualized by ¹³C NMR. Thecomparison of the NMR spectra of the respective homopolymers ofε-caprolactone and of d,l-lactide, with that of the copolymer formed,shows that the LL and CC sequences of the C═Os are associated withδ=173.3 ppm for the C═O of the polycaprolactone CC sequences andδ=169-169.8 ppm for the C═O of the d,l-polylactide.

No trace of copolymer is detected in the range of δ=170-173 ppm of therandom copolymers.

This specific distribution is confirmed by the ¹³C chemical shifts ofthe CHs and CH₂s for the same homopolymers and copolymers ofε-caprolactone (CCC etc.) and (LLL etc.). The presence of copolymer isbased on the fact that the ε-caprolactone chain end (CH₂OH) is notdetectable at δ=3.62 ppm in the copolymer produced after sequentialaddition of the two monomers in the order ε-caprolactone, d,l-lactide,whereas the signal at δ=4.4 ppm corresponding to the end-of-chain CH—OHof the open lactide is observed.

EXAMPLE 8 Preparation of a Polyglycolide Homopolymer

The reaction is carried out in acetone, which is the solvent for themonomeric glycolide. The composition of the initial mixture is 11.6 g(0.1 mol) of glycolide per 0.458 g (0.0033 mol) of TBD. The M/I molarratio is 30. The reaction is exothermic and a white precipitate formsimmediately as soon as room temperature has been reached and the firstfractions of TBD have been added. The mixture is brought to the refluxtemperature of acetone for two hours. The white solid is isolated byfiltration and the solvent is evaporated off under vacuum.

The NMR analysis (DMSO-D⁶ while hot) indicates the formation of apolyglycolide with the appearance of a singlet at δ=4.85 ppm. The CH₂OHchain end is identifiable at δ=4.10 ppm and gives a degree ofpolymolecularity of 30. The ¹³C NMR spectrum is characteristic of theformation of the polyglycolide, with regard to the chemical shift of themonomer, with a δ=166 ppm for the C═O; δ=60.4 ppm for the CH₂ and δ=59.2ppm for the CH₂OH, by ¹³C NMR.

The known insolubility of the polymer is verified. Only DMSO while hot,hexafluoropropanol and hexafluoroacetone are solubilizers of thepolymer.

EXAMPLE 9 Preparation of Polylactones and Functionalization in situ

9.1—Standard Experimental Protocol

The lactone is mixed with the functionalizing agent and the mixture ishomogenized at 80° C. After homogenization, the initiator is introducedall at once. The mixture is heated for 3 hours at 80° C. and then forone hour at 100° C. and finally for one and a half hours at 120° C. Thecrude reaction mixture is recovered and analyzed.

Examples 9.2 to 9.6 below illustrate the application of this protocol tothe production of functionalized polylactones.

9.2—Preparation of an ε-polycaprolactone and functionalization withethoxyethanol (simultaneous addition)

A functionalized ε-polycaprolactone is prepared in accordance with theprocedure described in 9.1, with 25 g (0.22 mol) of ε-caprolactone, 2.03g (0.0146 mol) of TBD and 1.98 g of ethoxyethanol. The M/I molar ratiois 15.

A crude sample is taken. The polymer is dissolved in 200 ml of CH₂Cl₂and 100 ml of water containing 2% of HCl. The organic phase is left tosettle out and then washed with 100 ml of water. The solvent isevaporated off, the remainder is take up with toluene, which is, inturn, evaporated off.

A washed sample is isolated.

The comparison of the NMR spectra of the crude product before and afterwashing and extraction indicates the presence of the ethoxyethoxy [sic]group in the chain of the ε-polycaprolactone: δ=1.2 ppm triplet of themethyl group; δ=4.2 ppm triplet of the OCH₂CH₂—O—CO group. The ¹H NMRspectrum more particularly contains the triplet at δ=4.23 ppm,characteristic of the protons of CH₂ of the ester of the ethoxyethanolgroup attached.

The GPC analysis gives:

Final Mn=980, final Mw=3800; Mn/Mw=3.88.

It is observed that, when increasing the M/I molar ratio (simultaneousreaction of 25 g of caprolactone, 1 g of ethoxyethanol and 1 g of TBD;the reaction is exothermic, the temperature reaches 65° C. at the timeof mixing), and for the same reaction time, a lower conversion rate,with more than 50% of residual caprolactone, is obtained. The masses ofthe crude polymer are Mn 3600 and Mw 7490; Mn/Mw=2.06.

9.3—Preparation of an ε-polycaprolactone and Functionalization withPolyoxyethylene Glycol 6000 (PEG 6000, Mean Hydroxyl Group Content5.3×10⁻³/g)

A polycaprolactone modified with PEG 6000 is prepared according to theprocedure described in Example 9.1. The monomer/initiator and PEG6000/initiator molar ratios are, respectively, 30 and 0.62. The initialmixture of 50.6 g (0.44 mol) of ε-caprolactone and 54.6 g of PEG 6000(9×10⁻³ mol) is brought to 60° C. 2.02 g (1.45×10⁻² mol) of TBD are thenadded in solid form, all at once. The reaction is exothermic and thetemperature reaches 75° C. The mixture is maintained at 80° C. for 3hours, then one hour at 100° C. and, finally, 1 h 30 at 120° C. Thecrude white product is isolated, which solidifies with cooling.

The NMR analysis reveals the structural elements of the polycaprolactoneas indicated in Example 1.1 and a signal for the CH₂CH₂ protons of thepolyoxyethylene at δ=3.64 ppm. The signal at δ=4.2 ppm, characteristicof the protons of the CH₂ of the ester derived from the coupling of thePEG 6000 and of the polycaprolactone, is identified.

The SEC analysis gives the molecular masses Mn=9500 and Mw=10800 and apolydispersity index Mn/Mw=1.14.

9.4—Preparation of an ε-polycaprolactone and functionalization withpolyoxyethylene glycol 20000 (PEG 20000, hydroxyl group content 1.6×10⁻³molar).

The abovementioned standard procedure is carried out with 25.3 g (0.22mol) of ε-caprolactone, 91 g of PEG 20000 (4.55×10⁻³ mol) and 1.01 g(0.0073 mol) of TBD. The monomer/initiator and PEG 20000/initiator molarratios are, respectively, 30 and 0.62. The crude product is isolated,which solidifies with cooling.

The NMR analysis reveals the structural elements of the polycaprolactoneas indicated in Example 1.1 and a PEG CH₂CH₂ signal at δ=3.64 ppm. Avery weak signal at δ=4.2 ppm, characteristic of the protons of the CH₂of the ester formed by coupling of the alcohol function of the PEG andof the polycaprolactone, is identified.

9.5—Preparation of an ε-polycaprolactone and Functionalization with aPEG 20000-xanthan gum mixture

The standard procedure of Example 9-1 is carried out, with an initialmixture consisting of 35 g (0.31 mol) of ε-caprolactone, 91 g of PEG20000 (4.55 mol×10⁻³ mol) and 2 g of xantham gum. The internaltemperature of the mixture is brought to 60° C. and 1.39 g (10⁻² mol) ofTBD are added. The monomer/initiator and PEG 20000/initiator molarratios are, respectively, 30 and 0.45. The crude product is isolated,which solidifies with cooling.

The viscose behavior of the aqueous solution is demonstrated byrheological measurement on a Rheomat 30. The value of the shear strain,measured on a 6% aqueous solution, reaches 500 Pa at 10 s⁻¹ of shearrate. On FIG. 3, the curve of shear strain as a function of the shearrate demonstrates a rheofluidizing effect.

EXAMPLE 10 Preparation of Polylactones and Functionalization, Accordingto a Sequenced Method

10.1—Standard Experimental Protocol

The lactone is heated to 80° C. After homogenization of the lactone, theinitiator is added. For the polymerization, the mixture is heated for 3hours at 80° C. Next, the functionalizing agent is added, and then themixture is brought to 100° C. for one hour and to 120° C. for one and ahalf hours. The crude reaction mixture is recovered and analyzed.

Examples 10.2 to 10.7 below illustrate the application of this protocolto the production of functionalized polylactones.

10.2—Preparation of an ε-polycaprolactone and Functionalization withButanol (Sequenced Addition)

A polylactone is prepared in accordance with the procedure described in1.1, with 11.4 g (0.1 mol) of ε-polycaprolactone and 2.78 g (0.02 mol)of TBD. The M/I molar ratio is 20.

The reactor, equipped with a cooler, is maintained at 80° C. for 3hours. The viscose polymer is treated with 3.6 g of butanol (0.05 mol).The reaction time is prolonged by bringing the heating oil bath to 100°C. for one hour and then to 120° C. for one and a half hours.

The NMR spectrum of the crude product after washing and extraction withmethylene chloride indicates the presence of the butoxy segment in thechain of the ε-polycaprolactone (δ=0.92 ppm triplet of the methylgroup). The NMR of the carbonyl (C═O) indicates two types of C═O: theC═O of the polycaprolactone at δ=173.3 ppm and the C═O of the n-butoxyester at δ=173.1 ppm.

The degree of functionalization evaluated by NMR is 46%.

The SEC analysis gives the following results:

Before addition of the butanol, initial Mn=4400, initial Mw=10200;Mn/Mw=2.32,

After addition of the butanol, final Mn=1350, final Mw=3650; Mn/Mw=2.69.

10.3—Preparation of an ε-polycaprolactone and Functionalization withEthoxyethanol (Sequenced Addition)

A polycaprolactone is prepared in accordance with the proceduredescribed in 1.1, with 25 g (0.22 mol) of ε-caprolactone and 2.03 g(0.0146 mol) of TBD. The M/I molar ratio is 15.

The reaction is exothermic and the temperature reaches 65° C. The mediumbecomes viscose. The reactor is brought to 80° C. for 3 hours. Theviscose polymer is treated with 1.98 g of ethoxyethanol (0.022 mol). Thereaction time is prolonged by bringing the heating oil bath to 100° C.for one hour and then to 120° C. for one and a half hours. The crudesample is removed. The polymer is dissolved in 200 ml of CH₂Cl₂ and 100ml of water containing 2% of HCl. The organic phase is left to settleout and then washed with 100 ml of water. The solvent is evaporated offand the remainder is taken up with toluene, which is, in turn,evaporated off.

The comparison of the NMR spectra of the crude product before and afterwashing and extraction indicates the presence of the ethoxyethoxy [sic]group in the chain of the ε-polycaprolactone: δ=1.2 ppm triplet of themethyl group; δ=4.2 ppm triplet of the OCH₂CH₂—O—CO group. The ¹H NMRspectrum more particularly contains the triplet at δ=4.23 ppm,characteristic of the protons of CH₂ of the ester of the ethoxyethanolgroup attached.

The degree of functionalization is evaluated at 70%.

The ¹³C NMR analysis of the COs shows the presence of the COs of thepolycaprolactone at δ=173.27 ppm and the ester CO linked to the butoxysegment at δ=173.12 ppm.

The SEC analysis gives the following results:

Before addition of the ethoxyethanol: initial Mn=3600, initial Mw=12900;Mn/Mw=3.53;

After addition of the ethoxyethanol: final Mn=1160, final Mw=3790;Mn/Mw=3.25.

10.4—Preparation of an ε-polycaprolactone and Functionalization withAllylamine (Sequenced Addition)

A polycaprolactone is prepared in accordance with the proceduredescribed in 1.1, with 25 g (0.22 mol) of ε-caprolactone and 3.04 g(0.022 mol) of TBD. The M/I molar ratio is 10.

The reaction is exothermic and the temperature reaches 65° C.

The medium becomes viscose. The reactor is brought to 80° C. for 3hours. The viscose polymer is treated with 1.25 g of allylamine (0.022mol). The reaction time is prolonged by bringing the heating oil bath to100° C. for one hour and then to 120° C. for one and a half hours. Thecrude sample is removed. The polymer is dissolved in 200 ml of CH₂Cl₂and 100 ml of water/2% of HCl. The organic phase is left to settle outand then washed with 100 ml of water. The solvent is evaporated off andthe remainder is taken up with toluene, which is, in turn, evaporatedoff.

The ¹H NMR analysis indicates the characteristic presence of the protonsof the allyl group in the form of an unresolved peak consisting of anunresolved peak at δ=5.1 ppm for the CH₂ α of the double bond and acomplex unresolved peak at δ=5.6-5.9 ppm for the protons on the doublebond. The ¹³C NMR analysis gives δ_(C═O)=173.510 ppm for the C═O groupof the polycaprolactone and δ_(C═O)=172.583 ppm for the C═O of thecoupling group O═C—NH.

The NMR integration ratio of the end-of-chain CH₂ to the rest of thepolycaprolactone indicates a degree of polymolecularity of 6.

The SEC indicates a polymer free of monomer and of allylamine.

10.5—Preparation of an ε-polycaprolactone and Functionalization withMethoxyethylamine (Sequenced Addition)

A polycaprolactone is prepared in accordance with the proceduredescribed in 1.1, with 25 g (0.22 mol) of ε-caprolactone and 3.04 g(0.022 mol) of TBD. The M/I molar ratio is 1/10.

The reaction is exothermic. The medium becomes viscose.

The reactor is brought to 80° C. for 3 hours. The viscose polymer istreated with 1.65 g of methoxyethylamine (0.022 mol). The reaction timeis prolonged by bringing the heating oil bath to 100° C. for one hourand then to 120° C. for one and a half hours. The crude sample isremoved. The polymer is dissolved in 200 ml of CH₂Cl₂ and 100 ml ofwater. The organic phase is left to settle out and then washed with 100ml of water. The solvent is evaporated off and the remainder is taken upwith toluene, which is, in turn, evaporated off.

The ¹H NMR analysis indicates the characteristic presence of the protonsof the methoxy group in the form of a singlet at δ=3.36 ppm (CH₃O ). Thecarbonyl of the amide group (CO—NH) appears at δ=173.735 ppm close tothe carbonyl of the polycaprolactone at δ=173.5 ppm.

The NMR integration ratio of the end-of-chain CH₂ to thepolycaprolactone residue indicates a degree of polymolecularity of 6.

The SEC indicates a polymer free of monomer.

10.6—Preparation of an ε-polycaprolactone and Functionalization withDecylamine (Sequenced Addition)

A polycaprolactone is prepared with 25 g (0.22 mol) of ε-caprolactoneand 0.1 g (0.0073 mol) of TBD. The M/I molar ratio is 30.

The reaction is exothermic. The medium becomes viscose. The reactor isbrought to 80° C. for 3 hours. The viscose polymer is treated with 3.45g of decylamine (0.0022 mol). The reaction time is prolonged by bringingthe heating oil bath to 100° C. for one hour and then to 120° C. for oneand a half hours. The crude sample is removed. The polymer is dissolvedin 200 ml of CH₂Cl₂ and 100 ml of water. The organic phase is left tosettle out and then washed with 100 ml of water. The solvent isevaporated off and the remainder is taken up with toluene, which is, inturn, evaporated off.

The ¹H NMR analysis indicates the characteristic presence of the protonsof the CH₃ group, δ=0.9 ppm in the form of a triplet. The presence ofthe CH₂ groups of the amine modifies the unresolved peak of the CH₂s atδ=1.7 ppm. The amide carbonyl group is identified by ¹³C NMR at δ=172.47ppm, close to the C═O group of the polycaprolactone at δ_(C═O)=173.18ppm.

The integration ratio of the end of chain to the polycaprolactoneresidue indicates a degree of polymerization (determined by SEC) of 33before functionalization, and of 22 after treatment with decylamine. Thelevel of attachment assessed by NMR is 70%.

The SEC indicates a polymer free of monomer.

The SEC (THF) analysis gives the following results:

After addition of the decylamine: final Mn=3700 and final Mw=8600;Mn/Mw=2.32.

10.7—Preparation of an ε-polycaprolactone and Functionalization withTetraethylene Glycol 200 (TEG, M=194, Mean Hydroxyl Group Content 0.16eq./g) (Sequenced Addition)

A polycaprolactone modified with TEG-200 is prepared according to thesequential method described in 10.1.

The monomer/initiator molar ratio is 30; that of TEG 200/initiator is0.89. 35 g (0.31 mol) of ε-caprolactone are brought to 60° C. and 1.39 g(0.01 mol) of TBD in solid form is added all at once. The reaction isexothermic and the temperature reaches 75° C. The temperature ismaintained at 80° C. for three hours. The ε-caprolactone polymerizes andthe medium becomes pasty. 1.71 g (0.89×10⁻² mol) of TEG are added. Themixture is brought to 100° C. for one hour and then to 120° C. for 1 h30. A slightly pink crude product is isolated, which solidifies withcooling.

The NMR analysis reveals the structural elements of the polycaprolactoneas indicated in Example 1.1 and a signal for the CH₂CH₂ protons of thetetraoxyethylene at δ=3.64 ppm (multiplet). The signal, at δ=4.2 ppm(triplet), characteristic of the protons of the CH₂ of the ester derivedfrom coupling TEG-200 and polycaprolactone, is identified. The completeelimination of the initiator by washing is noted.

The SEC analysis gives a single distribution of molecular massesMn=10900 and Mw=29000, i.e. a polydispersity index Mn/Mw=2.6, for thepolylactone before functionalization, and Mn=4400 and Mw=9300 and apolydispersity index Mn/Mw=2.1, for the polycaprolactone functionalizedwith TEG-200.

In a second test, an equivalent amount of the crude polymer is dissolvedin 100 ml of CH₂Cl₂ and washed with 100 ml of 3N HCl followed with 100ml of water. The emulsified mixture is left to settle out and theorganic phase is recovered, which organic phase is dried and thenevaporated, under vacuum for two hours under 10⁻¹ mm Hg. The whitepolymer solidifies. The NMR analysis indicates an absence of theinitiator.

EXAMPLE 11 Preparation of Polylactides and Functionalization, in situ

11.1—Standard Experiment Protocol

The lactide is mixed with the functionalizing agent and the mixture ishomogenized at 80° C. After homogenization, the initiator is introducedall at once. The mixture is heated for 3 hours at 80° C., then for onehour at 100° C. and finally for one and a half hours at 120° C. Thecrude reaction mixture is recovered and analyzed.

Examples 11.2 to 11.4 below illustrate the application of this protocolto the production of a functionalized polylactide.

11.2—Polymerization of a (D,L)-lactide and Functionalization with a PEG10000

The standard procedure of Example 11-1 is carried out, with an initialmixture of 5.8 g (0.05 mol) of (D,L)-lactide and 8 g of PEG 10000(0.8×10⁻³ mol). The internal temperature of the mixture is brought to60° C. and 280 mg (2.01×10⁻³ mol) of TBD are added. Themonomer/initiator and PEG 10000/initiator molar ratios are,respectively, 25 and 0.40. A brittle white solid is isolated.

The NMR spectrum (CHCl₃) shows the characteristic elements at δ=1.57 ppm(CH₃, unresolved peak); δ=5.17 ppm (O—CHCH₃, multiplet), δ=4.32 ppm(CH₂CH₂—OCO, multiplet), δ=4.36 ppm (HO—CH—CH₃, quartet), δ=10.3 ppm(COOH). The NMR analysis indicates the presence of a lactide-PEGcoupling ester group and polylactide/OH chain end/COOH chain endabundance residues of 0.035/0.038/0.032.

The SEC measurement of the molecular masses gives Mn=15300, Mw=17300 andMn/Mw=1.13.

The product dissolved in CH₂Cl₂ and then washed with water acidifiedwith HCl (pH=3) gives (D,L)-polylactide-PEG free of TBD.

11.3—Polymerization of an (L)lactide and Functionalization with a PEG10000

The procedure of Example 11-1 is carried out, with an initial mixture of2.9 g (0.025 mol) of (L)lactide and 6 g of PEG 10000 (0.6×10⁻³ mol). Theinternal temperature of the mixture is brought to 60° C. and 139 mg(10⁻³ mol) of TBD are added. The monomer/initiator and PEG10000/initiator molar ratios are, respectively, 25 and 0.60. A brittlewhite solid is isolated.

The NMR spectrum gives the characteristic elements at δ=1.57-9 ppm (CH₃,doublet); δ=5.15-7 ppm (O—CHCH₃, doublet), δ=4.32 ppm (CH₂CH₂—OCO,multiplet), δ=4.36 ppm (HO—CH—CH₃, quartet), δ=10.3 ppm (COOH). The NMRanalysis clearly indicates the presence of a lactide-PEG coupling estergroup and (L)-polylactide-PEG ester/OH chain end/COOH chain endabundance ratios of 0.068/0.049/0.043.

The SEC measurement of the molecular masses gives Mn=14400, Mw=16600 andMn/Mw=1.15.

The crude product dissolved in CH₂Cl₂ and then washed with wateracidified with HCl (pH=3) gives (L)-polylactide-PEG free of TBD.

11.4—Polymerization of (D,L)-lactide-glycolide and Functionalizationwith a PEG 10000.

A procedure modified from Example 11-1 is carried out. The initialmixture contains 3.5 g (2.2×10⁻² mol) of (D,L)-lactide and 4 g of PEG10000 (0.4×10⁻³ mol). The mixture is brought to 60° C. and 0.28 g(2×10⁻³ mol) of initiator TBD is added. The polymerization-graftingreaction is carried out to its end according to the protocol of Example1.1. The temperature is brought back to 50° C. at the end of thereaction and 2.2 g (1.9×10⁻² mol) of glycolide are added, which reactinstantaneously. The mixture is maintained for 30 min at 80° C. and thehard and brittle slightly yellow solid is isolated.

The NMR analysis shows the elements characteristic of thepoly(D,L)-lactide (δ=5.18 ppm) and of the PEG at δ=3.63 ppm, the CH₂characteristic of an ester coupling group at δ=4.2-4.3 ppm (in the formof a multiplet), the singlet signal of the polyglycolide at δ=4.8 ppm(CH₂OCO) and of its end-of-chain CH₂ at 4.28 ppm (CH₂OH). The blockpolymer is relatively insoluble in organic solvents; it solubilizes inchloroform and DMSO while hot.

EXAMPLE 12 Preparation of Polylactides and Functionalization, Accordingto a Sequenced Method

12.1—Standard Experimental Protocol

The lactide is heated to 80° C. After homogenization of the lactone, theinitiator is added. For the polymerization, the mixture is heated at 80°C. for 3 hours. Next, the functionalizing agent is added and the mixtureis then brought to 100° C. for one hour and to 120° C. for one and ahalf hours. The crude reaction mixture is recovered and analyzed.

Example 12.2 below illustrates the application of this protocol to theproduction of functionalized polylactides.

12.2—Preparation of a Polylactide and Functionalization withEthoxyethanol (Sequenced Addition)

The same procedure as that described in Example 12.1 is carried out,with 2.88 g (0.02 mol) of lactide, 185 mg of TBD and 1.8 g ofethoxyethanol (0.02 mol). The M/I molar ratio is 15. Addition of theinitiator all at once causes solubilization and an increase intemperature up to 38° C. After the reaction has been allowed to proceedfor two hours at 90° C., the solution becomes slightly red-brown. Thecrude sample is analyzed and the sample is washed as above.

The ¹³C NMR spectrum comprises a C═O at δ=172.416 ppm (C═O of thepolycaprolactone), a C═O at δ=172.622 ppm (C═O coupled to the initiator)and a weak C═O at δ=172.224 ppm (assigned to the C═O of theethoxyethanol ester).

What is claimed is:
 1. A process for producing oxacarbonylated polymers,reacting at least a monomer comprising at least one cyclic oxacarbonylfunction, and an initiator and polymerizing or copolymerization saidmonomer in bulk or in solution to produce oxacarbonylated polymers,wherein the initiator is chosen from the bicyclic guanidine compoundscorresponding to formula (I) or (II)

and from the bicyclic guanidine compounds corresponding to formula (I)in which at least any one of positions 2, 3, 4, 8, 9 and 10 issubstituted and from the bicyclic biguanidine compounds corresponding toformula (II) in which at least any one of positions 2, 3, 7 and 8 issubstituted, said position at least being substituted with at least oneradical chosen from alkyl groups having from 1 to 6 carbon atoms,cycloalkyl groups having from 5 to 7 carbon atoms and thehydrocarbon-based chains of polystyrene.
 2. The process as claimed inclaim 1, wherein the initiator is7H-1,5,7-triazabicyclo(4.4.0)dec-5-ene.
 3. The process as claimed inclaim 1, wherein the cyclic oxacarbonyl function of the monomer is alactone function.
 4. The process as claimed in claim 3, wherein themonomer is selected from the group consisting of ε-caprolactone,δ-valerolactone, β-butyrolactone, γ-butyrolactone,2,6-dimethyl-1,4-dioxan-2,5-dione and 1,4-dioxan-2,5-dione.
 5. Theprocess as claimed in claim 1, wherein at least two different monomersare reacted.
 6. The process as claimed in claim 1, wherein the molarratio of the monomer(s) to the initiator ranges from 1 to
 500. 7. Theprocess as claimed in claim 1, wherein the reaction is performed at atemperature ranging from 0° C. to 150° C.
 8. The process as claimed inclaim 7, wherein the reaction is performed at a temperature ranging from50° C. to 120° C.
 9. The process as claimed in claim 7, wherein thepolymerization reaction is carried out in bulk or in a solvent selectedfrom the group consisting of tetrahydrofuran, toluene, and dibutylether.
 10. The process as claimed in claim 1, wherein a functionalizingagent is added to the monomer and to the initiator.
 11. The process asclaimed in claim 10, wherein the functionalizing agent is a linear orbranched molecule or macromolecule containing at least one alcoholfunction, one amine function or one ester function.
 12. The process asclaimed in claim 11, wherein the functionalizing agent is selected fromthe group consisting of butanol, ethoxyethanol, pentaerythritol,allylamine, methoxyethylamine, decylamine, ethoxyethanolamine and estersof carboxylic acids.
 13. The process as claimed in claim 11, wherein thefunctionalizing agent is a polymer or copolymer of alkylene glycol. 14.The process as claimed in claim 13, wherein the functionalizing agent isa copolymer of ethylene (PEG), propylene (PPG) or mixtures thereof. 15.The process as claimed in claim 10, wherein the functionalizing agent isa mixture of at least one alkylene glycol polymer and at least onepolyglucoside.
 16. The process as claimed in claim 10, wherein thepolymerization and the functionalization are carried out sequentially.17. The process as claimed in claim 10, wherein the polymerization andthe functionalization are carried out simultaneously in bulk or in asolvent.
 18. An oxacarbonylated polymer that is produced using a processas claimed in claim
 1. 19. An oxacarbonylated polymer that is producedusing a process as claimed in claim
 10. 20. A method for initiating thepolymerization or copolymerization of a monomer having at least oneoxacarbonyl function comprising: reactingf a bicyclic guanidine compoundcorresponding to formula (I) or (II)

 in which one and/or the other of the rings may be substituted, in atleast any one of positions 2, 3, 4, 8, 9 and 10 of formula (I) or in atleast any one of positions 2, 3, 7 and 8 of formula (II), with at leastone radical chosen from alkyl groups having from 1 to 6 carbon atoms,cycloalkyl groups having from 5 to 7 carbon atoms and thehydrocarbon-based chains of polystyrene, with monomers comprising atleast one cyclic oxacarbonyl function to initiate polymerization orcopolymerization of the monomer.
 21. The method as claimed in claim 20,wherein the bicyclic guanidine compound is7H-1,5,7-triazbicyclo(4,4,0)dec-5-ene.
 22. The process as claimed inclaim 1, wherein the molar ratio of the monomers to the initiator rangesfrom 1 to
 200. 23. The process as claimed in claim 11, wherein thefunctionalizing agent is chosen from polymers and copolymers of ethyleneglycol (PEG), mixtures of said polymers, mixtures of said copolymers andmixtures of said polymers and copolymers.